Antibodies to ticagrelor and methods of use

Abstract

The disclosure generally provides antibodies and antigen binding fragments of antibodies that bind ticagrelor and metabolites of ticagrelor. The disclosure also provides compositions comprising the antibodies, nucleic acid molecules encoding the antibodies, methods of treating a patient comprising administering the antibodies, and methods of making and using the antibodies.

We claim: 
     
       1. An antibody or a fragment thereof that specifically binds a cyclopentyltriazolopyrimidine compound of the Formula (Ia): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is selected from the group consisting of C 1 -C 6  alkoxy and C 1 -C 6  alkylthio, 
 R 2  is selected from the group consisting of H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and substituted C 3 -C 6  cycloalkyl, and 
 R 3  is selected from the group consisting of H, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, and C 1 -C 6  alkanol; 
 
       wherein the antibody or a fragment thereof comprises a combination of heavy chain variable region (VH) and light chain variable region (VL) sequences selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:7; SEQ ID NO:12 and SEQ ID NO:17; SEQ ID NO:22 and SEQ ID NO:27; SEQ ID NO:32 and SEQ ID NO:37; SEQ ID NO:42 and SEQ ID NO:47; SEQ ID NO:52 and SEQ ID NO:57; SEQ ID NO:62 and SEQ ID NO:67; and SEQ ID NO:72 and SEQ ID NO:77. 
     
     
       2. The antibody or a fragment thereof of  claim 1 , wherein the antibody comprises a combination of VH and VL selected from the group consisting of SEQ ID NO:52 and SEQ ID NO:57; SEQ ID NO:62 and SEQ ID NO:67; and SEQ ID NO:72 and SEQ ID NO:77. 
     
     
       3. An antibody or a fragment thereof that specifically binds a cyclopentyltriazolopyrimidine compound of the Formula (Ia): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is selected from the group consisting of C 1 -C 6  alkoxy and C 1 -C 6  alkylthio; 
 R 2  is selected from the group consisting of H, C 1 -C 6  alkyl, substituted C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl, and substituted C 3 -C 6  cycloalkyl; and 
 R 3  is selected from the group consisting of H, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, and C 1 -C 6  alkanol: 
 
       wherein the antibody or a fragment thereof comprises a combination of complementarity-determining regions (CDR) selected from the group consisting of:
 SEQ ID NO:53 (VH CDR1), SEQ ID NO:54 (VH CDR2), SEQ ID NO:55 (VH CDR3), SEQ ID NO:58 (VL CDR1), SEQ ID NO:59 (VL CDR2), and SEQ ID NO:60 (VL CDR3); 
 SEQ ID NO:63 (VH CDR1), SEQ ID NO:64 (VH CDR2), SEQ ID NO:65 (VH CDR3), SEQ ID NO:68 (VL CDR1), SEQ ID NO:69 (VL CDR2), and SEQ ID NO:70 (VL CDR3); and 
 SEQ ID NO:73 (VH CDR1), SEQ ID NO:74 (VH CDR2), SEQ ID NO:75 (VH CDR3), SEQ ID NO:78 (VL CDR1), SEQ ID NO:79 (VL CDR2), and SEQ ID NO:80 (VL CDR3). 
 
     
     
       4. The antibody of  claim 1  or  3 , wherein the antibody is selected from a monoclonal antibody, a humanized antibody, a human antibody, a single chain Fv (scFv), a Fab, a F(ab′) 2 , a single chain diabody, and an antibody mimetic.